CA2749280C - Methods for improving hepatic and immune function in an animal - Google Patents
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23K20/00—Accessory food factors for animal feeding-stuffs
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- A23K20/158—Fatty acids; Fats; Products containing oils or fats
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
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Abstract
The invention encompasses compositions and methods for improving animal health and in certain embodiments to compositions and methods for improving hepatic and immune function in aged felines.
Description
TITLE OF THE INVENTION
METHODS FOR IMPROVING HEPATIC AND IMMUNE FUNCTION IN AN ANIMAL
[001]
FIELD OF THE INVENTION
METHODS FOR IMPROVING HEPATIC AND IMMUNE FUNCTION IN AN ANIMAL
[001]
FIELD OF THE INVENTION
[002] The invention encompasses compositions and methods for improving animal health and in certain embodiments to compositions and methods for improving hepatic and immune function in aged felines.
BACKGROUND OF THE INVENTION
BACKGROUND OF THE INVENTION
[003] The liver is a vital organ and has an important role in most every bodily function of a mammal. In one role, the liver acts as a filtration system to protect other organs from the effects of toxin buildup. Toxins absorbed from the digestive system are removed from the blood by the liver before they can affect the rest of the body. The capacity of a xenobiotic such as a drug, therapeutic agent, or chemical to produce injury to a liver is known as hepatotoxicity. The xenobiotic is a pharmacologically or toxicologically active substance not indigenously produced and therefore foreign to an organism. Many industrial compounds, drugs and other therapeutic agents are well established as injurious to a liver. As mammals age, their capacity for the filtration and clearance of xenobiotics by the liver decreases. It is well known that as mammals age, especially companion animals, they encounter health problems that require drugs and other therapeutic agents. Since liver filtration and clearance decreases in such an aged animal, administration of such drugs and therapeutic agents to improve the health of the animal may have hepatotoxic effects.
[00941 R---Lipoic acid (CAS number .1200-22-2, also known as thioctic acid and 1õ2-dithiolarie-3-penumoie acid) naturally occurs in plant and animal tissues, where it is covalently bound to an t-:.-amino group of lysine residues. Lipoic acid is commercially available and is produced by companies such as BASF and Coons. Lipoic acid is commercially available as an essentially pure SR-ct lipoic acid or as a racemic mixture of lipoic acid isomers. In plants, lipoic acid is most abundant in spinach and potatoes while in animal tissues, lipoic acid is most abundant in the kidney and the heart_ R-ai-lipoic acid was first discovered in 1937 (See Snell et al.., journal. Ba.ct. 33; 207, 1937) and was not isolated =
and characterized until 195 (See Reed et at Science 114:94-4, 1951). R-Q-lipoic acid may be synthesized and such methods are well known in the art. (See U.S. Patent No. 2,890,716 tO Reed issued April 18, 1961). R-a:-lipoi.c acid has been classified as an antioxidant. and has been used in high dosages as a treatment for Type II diabetes. Studies have shown that mixtures of camitine and lipoic acid may enhance metabolism and alleviate oxidative stress. (See U.S. Patent No. 5,916)912 to Ames et al. issued Pant 29. 1999 and US, Patent No. 6,365,622 to C:avayzo issued. April 2, 2002.). In addition, it. has been shown that a companion animal diet comprising lipoic acid among other ingredients appears to inhibit the deterioration of the mental capacity of an aged companion animal.
(Seell,S. Patent Application Publication Nos. 2002/0076469, 2002/0052402, 2002/0076470, 2:000/115710, and 2:002/0119182).
100051 Studies have shown that mitochondri.al oxidation plays a role in the metabolism of lipoic acid, .Althoud the metabolism in humans mainly resembles that observed in mice and rats, the formation of oxidized structures related to tetranorlipoic acid found in canines appears to have no equivalent in humans. In addition, 3-ketolipoic acid, an intermediate in the mitochondria" oxidation. of lipoic acid has been reported in plasma samples from rats and humans but has not been found in plasma .from canines. (See Schupke, H.
etal. Drug.
Metabolism and Disposition, 29 (6) 855-862, 2001). it appears that the metabolic pathway.
of a-lipoic: acid is different in canines as compared to humans.
100061 Mercapturic acids are sulfur derivatives of .N-acetyl-cysteine, which is.
synthesized from glutathione (GSM. It. is generally accepted that most compounds are metabolized to mercapturic acids first undergo conjugation with C/SH catalyzed by an enzyme called glatathione S -tratisferase, found in the soluble or supernatant liver refractions. The menapturic acid pathway appears to have evolved as a protective mechanism against xenobiotic induced hepatotoxicity or carcinogenicity, serving .to detoxilv a large number of noxious substances that are inhaled, ingested or normally õ
produced metabolically every day: Lipoic acid not only up regulates the glutathione but also up regulates the enzyme, glutathione S-transfi'.,rase that conjugates nintathione in the liver. Bromosulfophthalein WAS number 71-6740 also known as BSP and sulfobromophthalein) is an organic dye that., viihen injected into the circulation, is removed.
by the liver at a rate that reflects the liver '..s ability to extract and metabolize a number of organic compounds. See S. M. Rosenthal, E.C. White, 3, Pharmacol, 24,265 (1924.) W.
Ilacki et al., J. Lab. Clin. Med. 88, 1019 (1976). BSI' is cleared from the liver in three steps. First. BSP is transferred. from albumin through the plasma to the .liver. This step is dependent on plasma protein concentration and other ligands that bind to plasma proteins, Secondly. BSP is complexed in the liver by a ligand and z. protein. Finally, BSP is conjugated by glutathione Via giutathione S-transferase enzyme and eliminated into the bile duct arid this is the rate-limiting step. Thus BSP is an example of a xenobiotic that when measured in the blood after injection, provides intermation on the functional capabilities of the liver.
SUMMARY OF THE INVENTION
[00071 The invention generally -encompasses compositions comprising an effective ainourn of :lipoic acid or a salt thereof; wherein said effective amount is effective in improving hepatic or immune function in an animal.
10008] in another embodiment, the invention encompasses methods for improving hepatic function in an animal in need thereof by feeding lipoic acid or a salt thereof to the animal, generally in a diet including lipoic acid or a salt. thereof' in an amount effective to improve In,patis,; function.
100091 In another embodiment, the invention encompasses methods for improving immune function in an animal in need thereof by feeding lipoic acid or a salt thereof to the animal, generally in a diet comprising lipoic acid or a salt thereof in an amount effective to improve immune function.
[0010] In various embodiments, the invention is a new approach for improving the health of aging animals, for example, felines, based upon the use of lipoic acid or a salt thereof as part of a diet that is fed to the animals.
[0010a] A further embodiment of the invention relates to a composition for use in improving immune function in a feline in need thereof, wherein the improvement in immune function comprises increasing lymphocyte proliferation, which composition comprises an effective amount of lipoic acid or a salt thereof, wherein said effective amount is effective in improving immune function in a feline.
[0010b] A further embodiment of the invention relates to a composition comprising an effective amount of lipoic acid or a salt thereof to improve immune function in a feline, wherein said effective amount of lipoic acid is 65 ppm, and wherein the improvement in immune function comprises increasing lymphocyte proliferation.
[0010c] A further embodiment of the invention relates to a composition comprising an effective amount of lipoic acid or a salt thereof to improve immune function in a feline, wherein said effective amount of lipoic acid is 650 ppm, and wherein the improvement in immune function comprises increasing lymphocyte proliferation.
[0011] Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the illustrative embodiments of the invention, are not intended to limit the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Figure 1 is a graphical representation illustrating that the inclusion of lipoic acid into foods at 65 ppm and 650 ppm for 6 weeks had no adverse effects on bodyweight for cats.
[00941 R---Lipoic acid (CAS number .1200-22-2, also known as thioctic acid and 1õ2-dithiolarie-3-penumoie acid) naturally occurs in plant and animal tissues, where it is covalently bound to an t-:.-amino group of lysine residues. Lipoic acid is commercially available and is produced by companies such as BASF and Coons. Lipoic acid is commercially available as an essentially pure SR-ct lipoic acid or as a racemic mixture of lipoic acid isomers. In plants, lipoic acid is most abundant in spinach and potatoes while in animal tissues, lipoic acid is most abundant in the kidney and the heart_ R-ai-lipoic acid was first discovered in 1937 (See Snell et al.., journal. Ba.ct. 33; 207, 1937) and was not isolated =
and characterized until 195 (See Reed et at Science 114:94-4, 1951). R-Q-lipoic acid may be synthesized and such methods are well known in the art. (See U.S. Patent No. 2,890,716 tO Reed issued April 18, 1961). R-a:-lipoi.c acid has been classified as an antioxidant. and has been used in high dosages as a treatment for Type II diabetes. Studies have shown that mixtures of camitine and lipoic acid may enhance metabolism and alleviate oxidative stress. (See U.S. Patent No. 5,916)912 to Ames et al. issued Pant 29. 1999 and US, Patent No. 6,365,622 to C:avayzo issued. April 2, 2002.). In addition, it. has been shown that a companion animal diet comprising lipoic acid among other ingredients appears to inhibit the deterioration of the mental capacity of an aged companion animal.
(Seell,S. Patent Application Publication Nos. 2002/0076469, 2002/0052402, 2002/0076470, 2:000/115710, and 2:002/0119182).
100051 Studies have shown that mitochondri.al oxidation plays a role in the metabolism of lipoic acid, .Althoud the metabolism in humans mainly resembles that observed in mice and rats, the formation of oxidized structures related to tetranorlipoic acid found in canines appears to have no equivalent in humans. In addition, 3-ketolipoic acid, an intermediate in the mitochondria" oxidation. of lipoic acid has been reported in plasma samples from rats and humans but has not been found in plasma .from canines. (See Schupke, H.
etal. Drug.
Metabolism and Disposition, 29 (6) 855-862, 2001). it appears that the metabolic pathway.
of a-lipoic: acid is different in canines as compared to humans.
100061 Mercapturic acids are sulfur derivatives of .N-acetyl-cysteine, which is.
synthesized from glutathione (GSM. It. is generally accepted that most compounds are metabolized to mercapturic acids first undergo conjugation with C/SH catalyzed by an enzyme called glatathione S -tratisferase, found in the soluble or supernatant liver refractions. The menapturic acid pathway appears to have evolved as a protective mechanism against xenobiotic induced hepatotoxicity or carcinogenicity, serving .to detoxilv a large number of noxious substances that are inhaled, ingested or normally õ
produced metabolically every day: Lipoic acid not only up regulates the glutathione but also up regulates the enzyme, glutathione S-transfi'.,rase that conjugates nintathione in the liver. Bromosulfophthalein WAS number 71-6740 also known as BSP and sulfobromophthalein) is an organic dye that., viihen injected into the circulation, is removed.
by the liver at a rate that reflects the liver '..s ability to extract and metabolize a number of organic compounds. See S. M. Rosenthal, E.C. White, 3, Pharmacol, 24,265 (1924.) W.
Ilacki et al., J. Lab. Clin. Med. 88, 1019 (1976). BSI' is cleared from the liver in three steps. First. BSP is transferred. from albumin through the plasma to the .liver. This step is dependent on plasma protein concentration and other ligands that bind to plasma proteins, Secondly. BSP is complexed in the liver by a ligand and z. protein. Finally, BSP is conjugated by glutathione Via giutathione S-transferase enzyme and eliminated into the bile duct arid this is the rate-limiting step. Thus BSP is an example of a xenobiotic that when measured in the blood after injection, provides intermation on the functional capabilities of the liver.
SUMMARY OF THE INVENTION
[00071 The invention generally -encompasses compositions comprising an effective ainourn of :lipoic acid or a salt thereof; wherein said effective amount is effective in improving hepatic or immune function in an animal.
10008] in another embodiment, the invention encompasses methods for improving hepatic function in an animal in need thereof by feeding lipoic acid or a salt thereof to the animal, generally in a diet including lipoic acid or a salt. thereof' in an amount effective to improve In,patis,; function.
100091 In another embodiment, the invention encompasses methods for improving immune function in an animal in need thereof by feeding lipoic acid or a salt thereof to the animal, generally in a diet comprising lipoic acid or a salt thereof in an amount effective to improve immune function.
[0010] In various embodiments, the invention is a new approach for improving the health of aging animals, for example, felines, based upon the use of lipoic acid or a salt thereof as part of a diet that is fed to the animals.
[0010a] A further embodiment of the invention relates to a composition for use in improving immune function in a feline in need thereof, wherein the improvement in immune function comprises increasing lymphocyte proliferation, which composition comprises an effective amount of lipoic acid or a salt thereof, wherein said effective amount is effective in improving immune function in a feline.
[0010b] A further embodiment of the invention relates to a composition comprising an effective amount of lipoic acid or a salt thereof to improve immune function in a feline, wherein said effective amount of lipoic acid is 65 ppm, and wherein the improvement in immune function comprises increasing lymphocyte proliferation.
[0010c] A further embodiment of the invention relates to a composition comprising an effective amount of lipoic acid or a salt thereof to improve immune function in a feline, wherein said effective amount of lipoic acid is 650 ppm, and wherein the improvement in immune function comprises increasing lymphocyte proliferation.
[0011] Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the illustrative embodiments of the invention, are not intended to limit the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Figure 1 is a graphical representation illustrating that the inclusion of lipoic acid into foods at 65 ppm and 650 ppm for 6 weeks had no adverse effects on bodyweight for cats.
[0013] Figure 2 illustrates the effect of inclusion of 65 ppm and 650 ppm in diets and time on Concanavalin A stimulation. There was no significant difference between the groups at the beginning of the study or at the end. However, the cats on the 65 ppm lipoic acid inclusion had a significant increase in Concanavalin A-activated lymphocyte proliferation compared to baseline. Cats on the 650 ppm also displayed an increase.
[0014] Figure 3 illustrates that phytohaemagglutinin (PHA) stimulation showed no significant difference between groups at beginning or end. The illustrative group administered 65 ppm lipoic acid had a significant increase in lymphocyte proliferation between baseline and 6 weeks of intervention.
[0015] Figure 4 illustrates Pokeweed Mitogen stimulation was different between groups (ANOVA P<0.05) at the beginning but not the end of the study. The group with the lowest starting mean was the 65 ppm group. Subsequently, lymphocyte proliferation in the group administered 65 ppm lipoic acid was significantly increased compared to baseline after 6 weeks time.
[0016] Figure 5a and 5b illustrate natural killer cell activity. Based on the illustrative studies, no significant changes were detected from baseline to end of study for the 10:1 4a stimulation rate; however, all p values were less than 0.1. All changes between baseline and end of study were significant for all groups at the ;SO: I stimulation rate..
10.0171 Figure 6 illustrates graphs for representative Cornet assays. Two illustrative assays were performed: (i) inherent DNA damage and (2) hydrogen peroxide challenged damage. .Analysis of the data showed that all head DNA for. -all diets increased significantly (P<0.05) over the duration of the study thr both. in addition, all tail -DNA tail length and Olive tail moments decreased during the duration of the study for both control and hydrogen peroxide challenged cornet tests. However, there were no significant differences between groups at either the beginning or end for any of the comet measures.
In addition, ANOVA analysis of the change over time (difference pre.-post) showed no significant difference via t--test for each. comet variable under comm.l and hydrogen peroxide challenge conditions.
[0018] The Figures are intended to exemplify the. general characteristics of the invention fbr the purposes of the description of such embodiments herein. The Figure may not precisely reflect the characteristics of any given embodiment and is not necessarily intended to define or limit specific embodiments within the scope of this invention.
DETAILED DESCRI PTIDN: OF THE. IN
Definitions [00191 The term 'animal" rneans any animal susceptible to or suffering from impaired.
liver function and in need of improved liver clearance of xenobiotie substances or an animal that could benefit from improved liver clearance of xenobiotic substances. An animal is "susceptible to"' a disease or condition if the animal exhibits symptoms that indicate that the animal is likely to develop the condition or disease: .An animal is "suffering from" a disease or condition it animal exhibits symptoms that are indicative that the animal has developed the condition or disease, [00201 As used. herein, the terms "lipoie acid or a salt thereof" includes, but is not limited to, for example, alpha-lipoic acid, a ra.cemic mixture oflipoic acids, a lipoate salt, ester, amide or derivative .thereof, for example as described in U.S. patent number 5,621,1 IT in various embodiments, the lipoic. acid can be administered in a composition comprising a wet or dry food composition, which may be in the forin of a moist food, dry food, supplement or treat. The lipoic acid may be incorporated therein or on the surface of any food composition, such as, by spraying or precipitation thereon or may be added to the diet by way of snack., supplement, treat or 'tithe liquid portion of the diet such as water or another 'fluid. The lipoie acid may be administered as a powder, solid or as a liquid including a. gel, An important aspect is that the atinnal be provided an effective amount of the lipoip acid to provide a positive effect. Typically, the source of iipuic acid or a salt -thereof is present in the composition in an amount of up to an amount which remains non-toxic to the animal, [0021] The phrase. "salt thereof" as used herein includes hut is not limited to salts of lipeic acid used in the pet tbod compositions.. Lipoic acid is acidic in nature and therefore is capable of thrilling base salts with various cations. Examples of such salts include alkali metal or alkaline earth metal salts and., particularly, calcium, magnesium, sodium lithium, zinc, potassium, and iron. salts, [0022] The term "older animal" means any animal susceptible to or suffering from impaired liver function and in need of improved liver clearance of xenObiotic substances or an animal that could benefit from improved liver clearance oi-s-xeriobiotie substances because of age, General Description [0023] The invention generally encompasses compositions CoMprising an effective amount of lipoic add or a salt thereof, .wherein. said effective amount is -effective in improving hepatic or immune function in an animal.
[00241 in certain embodiments, the effective amount is effective in improving hepatic.
function in an ariblifil, [00251 in other embodiments, the effective amount is effective in improving immune function in an animal.
[0014] Figure 3 illustrates that phytohaemagglutinin (PHA) stimulation showed no significant difference between groups at beginning or end. The illustrative group administered 65 ppm lipoic acid had a significant increase in lymphocyte proliferation between baseline and 6 weeks of intervention.
[0015] Figure 4 illustrates Pokeweed Mitogen stimulation was different between groups (ANOVA P<0.05) at the beginning but not the end of the study. The group with the lowest starting mean was the 65 ppm group. Subsequently, lymphocyte proliferation in the group administered 65 ppm lipoic acid was significantly increased compared to baseline after 6 weeks time.
[0016] Figure 5a and 5b illustrate natural killer cell activity. Based on the illustrative studies, no significant changes were detected from baseline to end of study for the 10:1 4a stimulation rate; however, all p values were less than 0.1. All changes between baseline and end of study were significant for all groups at the ;SO: I stimulation rate..
10.0171 Figure 6 illustrates graphs for representative Cornet assays. Two illustrative assays were performed: (i) inherent DNA damage and (2) hydrogen peroxide challenged damage. .Analysis of the data showed that all head DNA for. -all diets increased significantly (P<0.05) over the duration of the study thr both. in addition, all tail -DNA tail length and Olive tail moments decreased during the duration of the study for both control and hydrogen peroxide challenged cornet tests. However, there were no significant differences between groups at either the beginning or end for any of the comet measures.
In addition, ANOVA analysis of the change over time (difference pre.-post) showed no significant difference via t--test for each. comet variable under comm.l and hydrogen peroxide challenge conditions.
[0018] The Figures are intended to exemplify the. general characteristics of the invention fbr the purposes of the description of such embodiments herein. The Figure may not precisely reflect the characteristics of any given embodiment and is not necessarily intended to define or limit specific embodiments within the scope of this invention.
DETAILED DESCRI PTIDN: OF THE. IN
Definitions [00191 The term 'animal" rneans any animal susceptible to or suffering from impaired.
liver function and in need of improved liver clearance of xenobiotie substances or an animal that could benefit from improved liver clearance of xenobiotic substances. An animal is "susceptible to"' a disease or condition if the animal exhibits symptoms that indicate that the animal is likely to develop the condition or disease: .An animal is "suffering from" a disease or condition it animal exhibits symptoms that are indicative that the animal has developed the condition or disease, [00201 As used. herein, the terms "lipoie acid or a salt thereof" includes, but is not limited to, for example, alpha-lipoic acid, a ra.cemic mixture oflipoic acids, a lipoate salt, ester, amide or derivative .thereof, for example as described in U.S. patent number 5,621,1 IT in various embodiments, the lipoic. acid can be administered in a composition comprising a wet or dry food composition, which may be in the forin of a moist food, dry food, supplement or treat. The lipoic acid may be incorporated therein or on the surface of any food composition, such as, by spraying or precipitation thereon or may be added to the diet by way of snack., supplement, treat or 'tithe liquid portion of the diet such as water or another 'fluid. The lipoie acid may be administered as a powder, solid or as a liquid including a. gel, An important aspect is that the atinnal be provided an effective amount of the lipoip acid to provide a positive effect. Typically, the source of iipuic acid or a salt -thereof is present in the composition in an amount of up to an amount which remains non-toxic to the animal, [0021] The phrase. "salt thereof" as used herein includes hut is not limited to salts of lipeic acid used in the pet tbod compositions.. Lipoic acid is acidic in nature and therefore is capable of thrilling base salts with various cations. Examples of such salts include alkali metal or alkaline earth metal salts and., particularly, calcium, magnesium, sodium lithium, zinc, potassium, and iron. salts, [0022] The term "older animal" means any animal susceptible to or suffering from impaired liver function and in need of improved liver clearance of xenObiotic substances or an animal that could benefit from improved liver clearance oi-s-xeriobiotie substances because of age, General Description [0023] The invention generally encompasses compositions CoMprising an effective amount of lipoic add or a salt thereof, .wherein. said effective amount is -effective in improving hepatic or immune function in an animal.
[00241 in certain embodiments, the effective amount is effective in improving hepatic.
function in an ariblifil, [00251 in other embodiments, the effective amount is effective in improving immune function in an animal.
[0026] n angther embodiment, the effective amount is from 25 ppm. to .2600 ppm of lipoic acid or a salt thereof, 100271 in another embodiment, the effective amount is from 50 ppm to 1200 ppm of lipoic acid or a salt thereof.
[0028] In another embodiment, the effective amount is from 65 ppm TO 650 -ppm of tipoic acid or a salt thereof.
100291 In another ilm'nocliment,. the animal is a companion animal.
[00301 In another embodiment, the companion animal is a:feline, [0031 I In another eMbodiment, the composition is a food composition, [0032] in another embodiment, the food composition is suitable for a companion animal.
[0033] In another embodiment, the food compo9idon is extruded, [0034( In another em.bodiment.õ the food composition. is canned.
/00351 In another embodiment, the invention encompasses methods ter improving hepatic or immune function in an animal comprising feeding an effective amount of lipoic acid or a salt thereof to the animal, wherein said effective mount is effective in improving hepatic or immune function.
[00361 in certain embodiments, the methods are effective in improving hepatic function in an animal.
[0037] in other embodiments, the methods are effective in improving immune fUnction in an animal.
[0038] In another embodiment, the effective amount is from 25 ppm to 2600 ppm of lipoic acid or a: salt thereof..
100391 In another embodiment, the effective amount is from 50 ppm to 1200 ppm of lipoic acid or a salt thereof 10040] in another embodiment, the effective amount is from 65 .ppm to 650 ippm of hpoic acid or a salt thereof [00411 In another embodiment, the animal is a companion animal.
(0042) hi another embodiment, the companion animal is a feline.
[0043] in another embodiment, the lipoie acid is part of the animal's daily diet.
[0044] in another embodiment, the daily diet comprises lipoic acid in an amount of greater than 50 ppm on a dry weight basis, [0045] in another embodiment, the lipoic acid is fed to the animal in a food composition suitable for consumptign by the a:hi-mai.
100461 in another embodiment, the animal is an older animal.
[0047] Another embodiment encompasses a composition suitable for improving immune function in an animal comprising au amount of nutrients and greater than 50 ppm of lipoic acid, [0048] in certain embodiments, the composition is a food composition.
(0049] in other embodiments, the lb:xi composition is suitable for a companion animal, [0050] In another embodiment, the food composition is SUitabk for a feline, 100511 In another embodiment, the composition is extruded or canned.
Compositions of the invention.
(0052( One embodiment of the invention encompasses) compositions for companion animals includirm an effective amount of lipoic acid or a salt thereof to improve .hepatic or immune {Unction in an animal.
100531 The quantity of alpha-lipoic acid in the compositiona can vary from at least about 25 ppm, about SO ppm, about 100 ppm, about 200 ppm. about 300 ppm, about ppm, about 700 ppm, about 900 ppm., about 1100 ppm, about .1200 ppm, about ppm, about 1600 ppm, about 1800 ppmõ about 2.000 ppm., about 2200 ppm, about ppm, or about 2600 ppm.
100541 En various eTTA:InAtiMeritS, the range of lipoic acid that can be administered to cats is 25 ppm to 2600 ppm. In certain illustrative: embodiments, quantities can vary 65 ppm to an amount which remains nontoxic to the pet. In other embodiments, a range is 50 ppm. to 1200 .pro., In other a range is 65 ppm. to 650 ppm.
[0055] in various etnbodimentsõ a food composition comprising lipoic acid provides a substantially nutritionally complete diet for the intended recipient animal.
.A "nutritionally complete diet" is a diet that includes sufficient nutrients for maintenance of normal health of a healthy animal on thediet.
[0028] In another embodiment, the effective amount is from 65 ppm TO 650 -ppm of tipoic acid or a salt thereof.
100291 In another ilm'nocliment,. the animal is a companion animal.
[00301 In another embodiment, the companion animal is a:feline, [0031 I In another eMbodiment, the composition is a food composition, [0032] in another embodiment, the food composition is suitable for a companion animal.
[0033] In another embodiment, the food compo9idon is extruded, [0034( In another em.bodiment.õ the food composition. is canned.
/00351 In another embodiment, the invention encompasses methods ter improving hepatic or immune function in an animal comprising feeding an effective amount of lipoic acid or a salt thereof to the animal, wherein said effective mount is effective in improving hepatic or immune function.
[00361 in certain embodiments, the methods are effective in improving hepatic function in an animal.
[0037] in other embodiments, the methods are effective in improving immune fUnction in an animal.
[0038] In another embodiment, the effective amount is from 25 ppm to 2600 ppm of lipoic acid or a: salt thereof..
100391 In another embodiment, the effective amount is from 50 ppm to 1200 ppm of lipoic acid or a salt thereof 10040] in another embodiment, the effective amount is from 65 .ppm to 650 ippm of hpoic acid or a salt thereof [00411 In another embodiment, the animal is a companion animal.
(0042) hi another embodiment, the companion animal is a feline.
[0043] in another embodiment, the lipoie acid is part of the animal's daily diet.
[0044] in another embodiment, the daily diet comprises lipoic acid in an amount of greater than 50 ppm on a dry weight basis, [0045] in another embodiment, the lipoic acid is fed to the animal in a food composition suitable for consumptign by the a:hi-mai.
100461 in another embodiment, the animal is an older animal.
[0047] Another embodiment encompasses a composition suitable for improving immune function in an animal comprising au amount of nutrients and greater than 50 ppm of lipoic acid, [0048] in certain embodiments, the composition is a food composition.
(0049] in other embodiments, the lb:xi composition is suitable for a companion animal, [0050] In another embodiment, the food composition is SUitabk for a feline, 100511 In another embodiment, the composition is extruded or canned.
Compositions of the invention.
(0052( One embodiment of the invention encompasses) compositions for companion animals includirm an effective amount of lipoic acid or a salt thereof to improve .hepatic or immune {Unction in an animal.
100531 The quantity of alpha-lipoic acid in the compositiona can vary from at least about 25 ppm, about SO ppm, about 100 ppm, about 200 ppm. about 300 ppm, about ppm, about 700 ppm, about 900 ppm., about 1100 ppm, about .1200 ppm, about ppm, about 1600 ppm, about 1800 ppmõ about 2.000 ppm., about 2200 ppm, about ppm, or about 2600 ppm.
100541 En various eTTA:InAtiMeritS, the range of lipoic acid that can be administered to cats is 25 ppm to 2600 ppm. In certain illustrative: embodiments, quantities can vary 65 ppm to an amount which remains nontoxic to the pet. In other embodiments, a range is 50 ppm. to 1200 .pro., In other a range is 65 ppm. to 650 ppm.
[0055] in various etnbodimentsõ a food composition comprising lipoic acid provides a substantially nutritionally complete diet for the intended recipient animal.
.A "nutritionally complete diet" is a diet that includes sufficient nutrients for maintenance of normal health of a healthy animal on thediet.
[0056j The lipoic acid or salt thereof is present at a concentration that is not deleterious to the intended animal's health. Thus, tor example, the lipoic acid or salt thereof is present at a concentration that does not cause undesirable or toxic effects, 100571 The composition can be a liquid or a solid food.. When the composition is a liquid, the hook acid or salt thereof can be admixed with other components.
Where the composition is solid, the lipoic acid may be coated on the composition, incorporated into the composition, or both, [00581 In various embodiments, the lipoic acid or salt thereof may be added to the animal's food. In certain embodiments, the lipoic acid or salt thereof may be added to the animal's food by a compounder or manufacturer at a site or by an. animal's caregiver prior to feeding the animal. In other embodiments, the lipoic acid or salt thereof may be added during the processing of an animal's food, such as dtaing and/or after mixing of other components of the composition that is then packaged and made available to consumers.
Such processing may include extrusion., canning, baking, and the like or any other method or process of producing pet foods that is known in the art. In other embodiments, the.
lipoic acid or salt thereof may be contributed by a natural source like an animal or plant component, or the lipoic acid or salt thereof may be contributed bi a synthetically derived source, or the lipoic acid or salt thereof may be contributed by a mixture of natural and synthetic sources, [00591 The compositions in addition to hock acid or a salt thereof include at least one component suitable. ter ccinsumption by a. companion. animal including, but not limited to, fats, carbohydrates, proteins, fibers, nutritional balancing agents such as vitamins, minerals, and trace elements, and mixtures thereof One of ordinary skill in the art can select the amount and type of food ingredients for a typical food based upon the dietary requirements of the animal, for example, the animal's species, age, size, weight, health, and function., [00601 The food ingredient part of the food .composition can include up to about 100%
of any particular food ingredient or can include a mixture of food ingredients in various proportions. In certain embodiments, the food composition includes a combination of food ingredients in amounts of 0 wt. % to .50 wt. fat, 0 wt. to 75 wt. %
carbohydrate, 0 wt.
Where the composition is solid, the lipoic acid may be coated on the composition, incorporated into the composition, or both, [00581 In various embodiments, the lipoic acid or salt thereof may be added to the animal's food. In certain embodiments, the lipoic acid or salt thereof may be added to the animal's food by a compounder or manufacturer at a site or by an. animal's caregiver prior to feeding the animal. In other embodiments, the lipoic acid or salt thereof may be added during the processing of an animal's food, such as dtaing and/or after mixing of other components of the composition that is then packaged and made available to consumers.
Such processing may include extrusion., canning, baking, and the like or any other method or process of producing pet foods that is known in the art. In other embodiments, the.
lipoic acid or salt thereof may be contributed by a natural source like an animal or plant component, or the lipoic acid or salt thereof may be contributed bi a synthetically derived source, or the lipoic acid or salt thereof may be contributed by a mixture of natural and synthetic sources, [00591 The compositions in addition to hock acid or a salt thereof include at least one component suitable. ter ccinsumption by a. companion. animal including, but not limited to, fats, carbohydrates, proteins, fibers, nutritional balancing agents such as vitamins, minerals, and trace elements, and mixtures thereof One of ordinary skill in the art can select the amount and type of food ingredients for a typical food based upon the dietary requirements of the animal, for example, the animal's species, age, size, weight, health, and function., [00601 The food ingredient part of the food .composition can include up to about 100%
of any particular food ingredient or can include a mixture of food ingredients in various proportions. In certain embodiments, the food composition includes a combination of food ingredients in amounts of 0 wt. % to .50 wt. fat, 0 wt. to 75 wt. %
carbohydrate, 0 wt.
=
lYti to 95 wt. '34 TYKAChl.:, 0 Wt. to 40 wt. % dietary fiber, and 0 wt. % to 15. wt. % of one or more nutritional balancing agents.
(0061) In certain embodiments, the fat and carbohydrate food ingredient is obtained from a variety Of sources such as animal fat, fish OIL vegetable oil, meat, meat by-products, grains, other animal or plant sources, and mixtures thereof Grains include wheat, corn, barley, and rice.
/00621 in certain embodiments, the protein .1-o:A ingredient is obtained from a variety sources such 4E; plants, animals, or both, Animal protein includes meat, meiq by-products, dairy, and eggs. Meats include the fleSh from poultry, fish, and animals such as cattle, swine, sheep, goats, and the like, meat by-products include lungs, kidneys, brain, livers, stomachs, and intestines. The protein food ingredient. may also be free. amino acids and/or peptides. Preferably, the protein food, ingredient includes meat, a meat by-product, dairy products, or eggs..
100631 in certain embodiments, the fiber food ingredient is obtained from a variety of sources such as vegetable fiber sources, for exampk, cellulose, beet pulp, peanut hulls, and soy fiber:
100641 In certain embodiments, the nutritional balancing agents are Obtained from a variety of sources known to skilled artisans, for example, .Vitainiii and mineral supplements and .food ingredients. Vitamins and minerals can be included in amounts required. to avoid.
deficiency and maintain health. These amounts are readily available in the art. The National Research Council (NRC) provides recommended amounts of such nutrients for farm animals. See, e,gõ 'Nutrient. Requirements of Swine (10th. Rev, Ed,, Nat'l. Academy Press, Wash., D.C., 1.998), 'Nutrient Requirements of Poultry (9th Rev, Edõ
Nat'l Academy Press, Wash, 1.994), 'Nutrient Requirements of Horses (5th Rev. Ed., Nat'l Academy Press, Wash. D.C., 1989), The American Feed Control Officials (...AAFC0) provides recommended amounts of such nutrients for doF:c and eats, Sec American Feed control.
Officials, Inc.., Official publication, pp. 129-1:37 (2004). Vitamins generally useful as food additives include vitamin A, vitamin B1, vitamin B2, vitamin 136, vitamin1312, vitamin D.
biotin, vitamin K. folic acid.. MositoL. niacin, and pantothenic acid.
Minerals and trace elements usefi.d as fOod additives include calcium, phosphorus, sodium, potassium, magnesium, eopper, zinc, chloride, iron, selenium, iodine, and iron.
Preparation of the Compositions of the Invention [00651 The compositions of the invention may be prepared in a canned or wet form using conventional food preparation processes known to skilled artisans.
Tyoicallyõ ground animal proteinaceous tissues are mixed with the other ingredients such as fish oils, cereal grains, balancing ingredients, special purpose additives (e.g., vitamin, and mineral mixtures, inorganic salts, cellulose and beet pulp, hulking agents, and the like) and water in amounts sufficient for processing. These ingredients are mixed in a vessel suitable for heating while blending the components. Heating of the mixture is effected using any suitable manner, for example, direct steam injection or using a vessel fitted with a beat exchanger. Following the addition of the last ingredient, the mixture is heated to a temperature of about 50. 'I' to about 212 CF. Temperatures outside this range are acceptable but. may be commercially impractical without use of other processing aids.
When heated to the appropriate temperature, the material will typically be in the limn of a thick. liquid. The thick liquid is filled into cans. A lid is applied, and the container is hermetically sealed. The sealed can is then placed. into conventional equipment designed to sterilize the contents. Sterilization is usually accomplished by beating to temperatures of greater than about 230 oF for an appropriate time depending on the temperature used, the composition, and similar factors. The compositions of the present invention can be added to the food compositions before, during, or after preparation.
[006 Food compositions may be prepared in a dry form .using conventional piycesses known to .skilled. artisans. Typically, dry ingredients such as animal protein, plant protein, grains, and the like are ground and mixed together. Moist or liquid ingredients, including fats, oils., animal protein, water, and the like are then added to and mixed with the dry mix..
'The mixture is then processed into kibbles or similar dry pieces. Kibble is often formed using an extrusion process in which the mixture of dry and -wet ingredients is subjected to.
mechanical work at a high pressure: and temperature and f3-.)reed through small openings and cut off into kibble by a rotating knife. The wet kibble is then dried and optionally coated with one or more topical coatings such as flavors, this. oils, powders, and the like.
Kibbk also can be made from the dough using a baking process, rather than extrusion, wherein the dough is placed into a mold beforf, dry-beat processing. The food compositions can be in the form of a treat using an extrusion or baking process similar to those described above for dry food or a. toy such as those disclosed in U.S.
Patent Nos.
5,339,771. and 5,419,2.83. The compositions of the present invention can be added to the.
-libod compositions before, during, or after preparation.
Methods of the Invention animals. The methods include feeding an amount of lipoic acid or a salt thereof effective to improve hepatic function to an animal in need thereof Generally, the lipoic acid is feed to the animal in amounts of 25 ppm to 2600 ppm, In certain illustrative embodiments, quantities can vary :from 25 ppm to 2600 ppm or to an amount which remains nontoxic. to the pet. In other embodiments, arange is 50 ppm. to 12.00 ppm. In other embodiments, a range is 65 ppm to 650 ppm.
[00681 The invention also encompasses methods for improving immune function in animals. The methods include feeding an amount of lipoic acid or a salt thereof in an amount effective to improvr., immune function to the animal in need thereof.
Generally, the lipoic acid is feed to the animal in amounts Of 25 ppm to 2600 ppm, in certain illustrative.
embodiments, quantities can vary from 25 ppm to 2600 ppm or to an amount which renwins nontoxic to the pet, In Other embodiments, a ranc,,,w is 50 ppm to 1200 ppm, In other embodiments, a range is 65 ppm to 650 ppm.
E0069] The methods of the invention include feeding an animal, for example, a companion animal such as a feline, a eeinpOSitiOn or diet containing lipoic acid or a salt thereof to improve hepatic function or immune function, particularly when these functions may be impaired by age, and to improve the overall health of the animal. The amount of lipoic acid given to the animal is a non-toxic amount, The lipoic acid may be either provided to the animal as a supplement or contained in a composition, including a diet, 1d to the animal. Such a supplement may be in the form of a pill or capsule, a treat or a biscuit, or any other edible form. By "diet," it is meant the food or drink regularly consumed by the animal, A diet may include supplements consumed. by the animal. A diet is considered to have essentially enough. nutrients to be life sustaining for the animal. A
companion animal diet can be any suitable pet food formula, which also provides adequate nutrition for the animal. For example, a typical feline diet for use in the present invention may contain from 8 to 50% fat, .16 to 50% by weight protein and. 3 to 15%
total dietary fiber. In another example,: a. typical feline diet may contain from 8 to .50%
by weight fat and from 30 to 60% by weiRht protein.. However, no specific. ratios or percentages of these or other nutrients are required. A nutrient is any food constituent that helps support life..
Nutrients important to an animal's health are known to skilled artisans, for example, proteins, carbohydrates, fats, fibers, vitamins, and minerals. Water is also vital to an animar3 health.
1.00701 Various embodiments of the mvention include a method for improving hepatic function or immune function in. an animal, particularly a companion animal., in such -embodiments, the method comprises feeding to the animal a composition, fbr example a diet, comprising lipoic acid or a salt thereof in an amount of at least 25 ppm on a dry matter basis. In still other embodiments, the method comprises feeding to the animal 4 diet comprising lipoic acid in an amount from 65 ppm to 650 ppm on a dry matter basis. As used herein, lipoic acid is in a raeemic mixture., but other embodiments may include lipoic acid which is essentially pure R-o, lipoic, acid or as a lipoate derivative, mixtures of isomers, salts, esters, amides or combinations thereof (For esamplc.: see US
Patent. No 5,621,177 to Bethge et al, issued April 15, 1997). in various embodiments, the range of lipoic acid that can be administered cats is 25 ppm to 2600 ppm in certain illustrative embodiments, quantities can vary from 65. ppm to 26.00 ppm or to an amount which remains nontoxic to the pet. in other embodiments, a range is 50 ppm to 1200 pprn, in other embodiments, a range 15 65 ppm to 650 ppm, 100711 in various embodiments, a. composition or diet comprising at least 25 .ppm.. to 2600 pprn of lipoic acid or a salt thereof. In some embodiments, the lipoic acid or salt thereof is added to the companion animal's food., In such embodiments, the lipoic acid or salt thereof may be added during the processing of the companion animal food that is then packaged and made available to consumers. Such prc3ceases may include extrusion., canning, baking and the like or any Other method or process of producing pet foods that is known in the art. In such processes, the lipoic acid may be contributed by a natural source.
like an animal or plant component, such as kidney or spinach or the lipoic acid may be -contributed by a synthetically derived source, or the lipoic acid may be contributed by a mixture crf natural and synthetic sources. In other embodiments, lipoic acid may he in a capsule forrn to be fed to the companion animal_ In still other embodiments, the lipoic acid or salt thereof may be in a powder or in a crystalline, which may be added to the animal's food or fed diredy -to the animal. In various embodiments, the companion animal diet comprises lipoic acid or sak thereof and other needed nutritional components.
In various ernbodim.ents, the companion. animal is a dog and in other embodiments, the companion animal is a cat, (00721 hi a further aspect, the present invention provides tOr a use of lipoic acid or salt thereof to prepare a medicament, in another, the invention provides for the use of lipoic acid to prepare a medicament for maintaining arid/or improving animal health, e.g., improving hepatic function or immune function in an animal by feeding an -amount of lipoic acid or a salt thereof' to the animal. Generally, medicaments are prepared by.
admixing a compound or composition with excipients, buffers, binders, plasticizers, colorants, diluents, compressing agents, lubricants, flavorants, moistening agents, and.
other ingredients known to skilled artisans to be useful for producing medicaments and formulating medicaments -that are suitable fin' administration to an animal.
[00731 In a further aspect, the invention provides kits suitable for feeding :lipoic acid or salt thereof to an animal. The kits comprise in. separate containers in a single package or in separate containers in a virtual paCkage, as appropriateõ lipoic acid and at least one of (I) one or more ingredients suitable for consumption by an animal, (2) instructions for how to combine the lipoic acid and other kit components to improve liver clearance ()fxeriobiotic _substances, particularly to produce a composition. -useful for improving liver clearance of xenobiotic substances, and (3) instructions for how to use the lipoic acid and other components of the present invention, particularly for the benefit of the animal., When the kit comprises a virtual package, the kit is limited to instructions in a virtual environment in combination with one or more physical kit. components. The kit contains the lipoic acid and other components in amounts sufficient to improve liver clearance of xenobiotic substances. Typically, the lipoic acid and the other suitable kit components are admixed j u.st prior to consumption by an animal. in one embodiment, the: kit contains a packet containing lipoic acid and a container of food lbr consumption by an animal, The kit may contain additional items such. as a device for mixing the lipoic acid. and ingredients or a device for containing the admixture, e.g., a food bowl. in another embodiment, the lipoic acid is mixed with additional nutritional supplements such as vitamins and minerals that promote good health in an animal.
/(0741 This invention is not limited to the particular methodology, protocols, and reagents described herein because they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to hmit the scope of the present invention, As used herein and M. die appended claims, the singular forms "aõ" "an," and "the" include plural reference unless the context clearly dictates otherwise. The terms "comprise", "comprises", and "comprising': are .to be interpreted inclusively rather than exclusively, ii)975) Unless defined otherwise, all echnical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of the invention. Although any methods and materials similar or equivalent to those described herein can. be used in the practice of the present invention, the preferred methods, devices, and materials are described herein.
[00761 All patents, patent applications, and publications mentioned. herein are incorporated herein by reference to the extent allowed by law fOr the purpose of describing and disclosing the compositions, compounds, methods, and similar information reported therein that might be used with the present invention, However, nothing herein is to be construed as an admission that the invention is not entitled to antedate such _disclosure by virtue of prior invention, EXAMPI,ES
[007 This invention can be Anther illustrated by the following examples of preferred embodiments thereof, although it will be understood that these examples are included merely fOr purposes of illustration and are not intended to limit the scope of the invention Unless otherwise specifically indicated, Example 1.
WON The study involved three groups of cats; Group I) cats on -a dry control Mod.
Group 2) cats on. a dry food fortified with approximately 65 ppm of lipoic acid, and Group 3) cats on a dry fOod fortified with approximately 650 ppm of lipoic acid on a dry Matter basis, All cats were fed control food for a two week baseline period at the end of which time iMITItine function assays were performed. One group of cats was then switched to the 65 ppm test food, one group to the 650 ppm test food and one group remained, on control and all were fed for another 6 weeks at which time the baseline teats were performed again, fOO-791 The administration of lipoic acid to old cats improved lymphocyte proliferation activity, which. may improve immune fanction. Most notably the effect of lipoi.c acid on improved lymphocyte proliferation in healthy cats at a .single level of inclusion (le, g 65 ppm).
100801 As illustrated in Figu.re 1, the inclusion of lipoic acid into feline pet foods at 65 ppm and 650 ppm for 6 weeks had no adverse effects on body-Nei& for cats.
lO08.11 Figure 2 illustrates the effect of inclusion of 65 ppm and 650 ppm in diets and time on Coneanavalin A. stimulation.. There was.. significant difference between the groups at the beginning of the study or at the end. However, the cats on the 65 ppm lipoic acid inclusion had a significant increase in Concanavalin A-activated lymphocyte proliferation compared to baseline. Cats on the 650 ppm also displayed an increase.
Accordingly, based on the Con.canavalin A-activated lymphocyte proliferation, the 11;
addition of 65 ppm or 650 ppm lipoic acid to a cat food composition could increase the immune response of cats.
100821 Figure 3 illustrates that pit,tohaemaplutinin (PHA) stimulation showed no significant difference between groups m beginning or end. The illustrative group administered 65 ppm lipoic acid had a significant increase in iyint-thocyte proliferation between baseline and 6 weeks of ifItVreetiti011. Accord-LI:1.0y, based on the PHA-activated lymphocyte proliferation, the addition of $5 ppm or 650 ppm. lipoic acid to a cat fbod composition could increase the immune response of cats [00831 Figure 4 illustrates Pokeweed Kitogen stimulation was different between groups (ANOVA P-(0.05) at the beginning. but not the end of the. study. The group with the lowest starting mean was the 65 ppm group. Subsequently,. lymphocyte proliferation in the group administered 65 ppm lipoic acid was significantly increased compared to baseline after 6 weeks time. Accordingly, based on the Pokeweed mitogen-activated lymphocyte proliferation, the addition of 65 ppm or 650 ppm lipoic acid to a cat fOod.
composition could increase the immune response of cats [00841 :Figure 5a and 5b illustrate natural killer cell activity. Based on the illustrative studies, no significant changes were detected from baseline to end of study for the 10:1 stimulation rate; however, all p values were less than 0.1: All changes betweenbaseline and end of study were significant for all groups at the 50:1 stimulation rate.
[00851 Figure 6 illustrates graphs for representative Comet assays. Iwo illustrative assays were performed: (1) inherent DNA damage and (2) .hydrogen peroxide challenged damage. Analysis of the data showed that all head DNA for all diets increased significantly (P<0.05) over the duration of the. study for both. In addition, all tail DNA tail length. and Olive tail momenta decreased during the duration of the study for both control and hydrogen peroxide challenged comet tests. However,. there were no significant differences between groups at either the beginning or end for any of the comet measures.
In addition, ANOVA analysis of the change over time (difilrence pre-post) showed no significant difkrence via t-test for each comet variable under control and hydrogen peroxide challenge conditions.
[00861 in the specification, there have been disclosed typical preferred embodiments of the invention and, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes-of limitation, the scope of the invention being set forth in the following. claims. Obviously many modifications and variations of the present invention are possible in light of the above teachings, it is therefore to be understood that within the scope of the appended claims the invention may be practiced otherwise than as specifically described,
lYti to 95 wt. '34 TYKAChl.:, 0 Wt. to 40 wt. % dietary fiber, and 0 wt. % to 15. wt. % of one or more nutritional balancing agents.
(0061) In certain embodiments, the fat and carbohydrate food ingredient is obtained from a variety Of sources such as animal fat, fish OIL vegetable oil, meat, meat by-products, grains, other animal or plant sources, and mixtures thereof Grains include wheat, corn, barley, and rice.
/00621 in certain embodiments, the protein .1-o:A ingredient is obtained from a variety sources such 4E; plants, animals, or both, Animal protein includes meat, meiq by-products, dairy, and eggs. Meats include the fleSh from poultry, fish, and animals such as cattle, swine, sheep, goats, and the like, meat by-products include lungs, kidneys, brain, livers, stomachs, and intestines. The protein food ingredient. may also be free. amino acids and/or peptides. Preferably, the protein food, ingredient includes meat, a meat by-product, dairy products, or eggs..
100631 in certain embodiments, the fiber food ingredient is obtained from a variety of sources such as vegetable fiber sources, for exampk, cellulose, beet pulp, peanut hulls, and soy fiber:
100641 In certain embodiments, the nutritional balancing agents are Obtained from a variety of sources known to skilled artisans, for example, .Vitainiii and mineral supplements and .food ingredients. Vitamins and minerals can be included in amounts required. to avoid.
deficiency and maintain health. These amounts are readily available in the art. The National Research Council (NRC) provides recommended amounts of such nutrients for farm animals. See, e,gõ 'Nutrient. Requirements of Swine (10th. Rev, Ed,, Nat'l. Academy Press, Wash., D.C., 1.998), 'Nutrient Requirements of Poultry (9th Rev, Edõ
Nat'l Academy Press, Wash, 1.994), 'Nutrient Requirements of Horses (5th Rev. Ed., Nat'l Academy Press, Wash. D.C., 1989), The American Feed Control Officials (...AAFC0) provides recommended amounts of such nutrients for doF:c and eats, Sec American Feed control.
Officials, Inc.., Official publication, pp. 129-1:37 (2004). Vitamins generally useful as food additives include vitamin A, vitamin B1, vitamin B2, vitamin 136, vitamin1312, vitamin D.
biotin, vitamin K. folic acid.. MositoL. niacin, and pantothenic acid.
Minerals and trace elements usefi.d as fOod additives include calcium, phosphorus, sodium, potassium, magnesium, eopper, zinc, chloride, iron, selenium, iodine, and iron.
Preparation of the Compositions of the Invention [00651 The compositions of the invention may be prepared in a canned or wet form using conventional food preparation processes known to skilled artisans.
Tyoicallyõ ground animal proteinaceous tissues are mixed with the other ingredients such as fish oils, cereal grains, balancing ingredients, special purpose additives (e.g., vitamin, and mineral mixtures, inorganic salts, cellulose and beet pulp, hulking agents, and the like) and water in amounts sufficient for processing. These ingredients are mixed in a vessel suitable for heating while blending the components. Heating of the mixture is effected using any suitable manner, for example, direct steam injection or using a vessel fitted with a beat exchanger. Following the addition of the last ingredient, the mixture is heated to a temperature of about 50. 'I' to about 212 CF. Temperatures outside this range are acceptable but. may be commercially impractical without use of other processing aids.
When heated to the appropriate temperature, the material will typically be in the limn of a thick. liquid. The thick liquid is filled into cans. A lid is applied, and the container is hermetically sealed. The sealed can is then placed. into conventional equipment designed to sterilize the contents. Sterilization is usually accomplished by beating to temperatures of greater than about 230 oF for an appropriate time depending on the temperature used, the composition, and similar factors. The compositions of the present invention can be added to the food compositions before, during, or after preparation.
[006 Food compositions may be prepared in a dry form .using conventional piycesses known to .skilled. artisans. Typically, dry ingredients such as animal protein, plant protein, grains, and the like are ground and mixed together. Moist or liquid ingredients, including fats, oils., animal protein, water, and the like are then added to and mixed with the dry mix..
'The mixture is then processed into kibbles or similar dry pieces. Kibble is often formed using an extrusion process in which the mixture of dry and -wet ingredients is subjected to.
mechanical work at a high pressure: and temperature and f3-.)reed through small openings and cut off into kibble by a rotating knife. The wet kibble is then dried and optionally coated with one or more topical coatings such as flavors, this. oils, powders, and the like.
Kibbk also can be made from the dough using a baking process, rather than extrusion, wherein the dough is placed into a mold beforf, dry-beat processing. The food compositions can be in the form of a treat using an extrusion or baking process similar to those described above for dry food or a. toy such as those disclosed in U.S.
Patent Nos.
5,339,771. and 5,419,2.83. The compositions of the present invention can be added to the.
-libod compositions before, during, or after preparation.
Methods of the Invention animals. The methods include feeding an amount of lipoic acid or a salt thereof effective to improve hepatic function to an animal in need thereof Generally, the lipoic acid is feed to the animal in amounts of 25 ppm to 2600 ppm, In certain illustrative embodiments, quantities can vary :from 25 ppm to 2600 ppm or to an amount which remains nontoxic. to the pet. In other embodiments, arange is 50 ppm. to 12.00 ppm. In other embodiments, a range is 65 ppm to 650 ppm.
[00681 The invention also encompasses methods for improving immune function in animals. The methods include feeding an amount of lipoic acid or a salt thereof in an amount effective to improvr., immune function to the animal in need thereof.
Generally, the lipoic acid is feed to the animal in amounts Of 25 ppm to 2600 ppm, in certain illustrative.
embodiments, quantities can vary from 25 ppm to 2600 ppm or to an amount which renwins nontoxic to the pet, In Other embodiments, a ranc,,,w is 50 ppm to 1200 ppm, In other embodiments, a range is 65 ppm to 650 ppm.
E0069] The methods of the invention include feeding an animal, for example, a companion animal such as a feline, a eeinpOSitiOn or diet containing lipoic acid or a salt thereof to improve hepatic function or immune function, particularly when these functions may be impaired by age, and to improve the overall health of the animal. The amount of lipoic acid given to the animal is a non-toxic amount, The lipoic acid may be either provided to the animal as a supplement or contained in a composition, including a diet, 1d to the animal. Such a supplement may be in the form of a pill or capsule, a treat or a biscuit, or any other edible form. By "diet," it is meant the food or drink regularly consumed by the animal, A diet may include supplements consumed. by the animal. A diet is considered to have essentially enough. nutrients to be life sustaining for the animal. A
companion animal diet can be any suitable pet food formula, which also provides adequate nutrition for the animal. For example, a typical feline diet for use in the present invention may contain from 8 to 50% fat, .16 to 50% by weight protein and. 3 to 15%
total dietary fiber. In another example,: a. typical feline diet may contain from 8 to .50%
by weight fat and from 30 to 60% by weiRht protein.. However, no specific. ratios or percentages of these or other nutrients are required. A nutrient is any food constituent that helps support life..
Nutrients important to an animal's health are known to skilled artisans, for example, proteins, carbohydrates, fats, fibers, vitamins, and minerals. Water is also vital to an animar3 health.
1.00701 Various embodiments of the mvention include a method for improving hepatic function or immune function in. an animal, particularly a companion animal., in such -embodiments, the method comprises feeding to the animal a composition, fbr example a diet, comprising lipoic acid or a salt thereof in an amount of at least 25 ppm on a dry matter basis. In still other embodiments, the method comprises feeding to the animal 4 diet comprising lipoic acid in an amount from 65 ppm to 650 ppm on a dry matter basis. As used herein, lipoic acid is in a raeemic mixture., but other embodiments may include lipoic acid which is essentially pure R-o, lipoic, acid or as a lipoate derivative, mixtures of isomers, salts, esters, amides or combinations thereof (For esamplc.: see US
Patent. No 5,621,177 to Bethge et al, issued April 15, 1997). in various embodiments, the range of lipoic acid that can be administered cats is 25 ppm to 2600 ppm in certain illustrative embodiments, quantities can vary from 65. ppm to 26.00 ppm or to an amount which remains nontoxic to the pet. in other embodiments, a range is 50 ppm to 1200 pprn, in other embodiments, a range 15 65 ppm to 650 ppm, 100711 in various embodiments, a. composition or diet comprising at least 25 .ppm.. to 2600 pprn of lipoic acid or a salt thereof. In some embodiments, the lipoic acid or salt thereof is added to the companion animal's food., In such embodiments, the lipoic acid or salt thereof may be added during the processing of the companion animal food that is then packaged and made available to consumers. Such prc3ceases may include extrusion., canning, baking and the like or any Other method or process of producing pet foods that is known in the art. In such processes, the lipoic acid may be contributed by a natural source.
like an animal or plant component, such as kidney or spinach or the lipoic acid may be -contributed by a synthetically derived source, or the lipoic acid may be contributed by a mixture crf natural and synthetic sources. In other embodiments, lipoic acid may he in a capsule forrn to be fed to the companion animal_ In still other embodiments, the lipoic acid or salt thereof may be in a powder or in a crystalline, which may be added to the animal's food or fed diredy -to the animal. In various embodiments, the companion animal diet comprises lipoic acid or sak thereof and other needed nutritional components.
In various ernbodim.ents, the companion. animal is a dog and in other embodiments, the companion animal is a cat, (00721 hi a further aspect, the present invention provides tOr a use of lipoic acid or salt thereof to prepare a medicament, in another, the invention provides for the use of lipoic acid to prepare a medicament for maintaining arid/or improving animal health, e.g., improving hepatic function or immune function in an animal by feeding an -amount of lipoic acid or a salt thereof' to the animal. Generally, medicaments are prepared by.
admixing a compound or composition with excipients, buffers, binders, plasticizers, colorants, diluents, compressing agents, lubricants, flavorants, moistening agents, and.
other ingredients known to skilled artisans to be useful for producing medicaments and formulating medicaments -that are suitable fin' administration to an animal.
[00731 In a further aspect, the invention provides kits suitable for feeding :lipoic acid or salt thereof to an animal. The kits comprise in. separate containers in a single package or in separate containers in a virtual paCkage, as appropriateõ lipoic acid and at least one of (I) one or more ingredients suitable for consumption by an animal, (2) instructions for how to combine the lipoic acid and other kit components to improve liver clearance ()fxeriobiotic _substances, particularly to produce a composition. -useful for improving liver clearance of xenobiotic substances, and (3) instructions for how to use the lipoic acid and other components of the present invention, particularly for the benefit of the animal., When the kit comprises a virtual package, the kit is limited to instructions in a virtual environment in combination with one or more physical kit. components. The kit contains the lipoic acid and other components in amounts sufficient to improve liver clearance of xenobiotic substances. Typically, the lipoic acid and the other suitable kit components are admixed j u.st prior to consumption by an animal. in one embodiment, the: kit contains a packet containing lipoic acid and a container of food lbr consumption by an animal, The kit may contain additional items such. as a device for mixing the lipoic acid. and ingredients or a device for containing the admixture, e.g., a food bowl. in another embodiment, the lipoic acid is mixed with additional nutritional supplements such as vitamins and minerals that promote good health in an animal.
/(0741 This invention is not limited to the particular methodology, protocols, and reagents described herein because they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to hmit the scope of the present invention, As used herein and M. die appended claims, the singular forms "aõ" "an," and "the" include plural reference unless the context clearly dictates otherwise. The terms "comprise", "comprises", and "comprising': are .to be interpreted inclusively rather than exclusively, ii)975) Unless defined otherwise, all echnical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of the invention. Although any methods and materials similar or equivalent to those described herein can. be used in the practice of the present invention, the preferred methods, devices, and materials are described herein.
[00761 All patents, patent applications, and publications mentioned. herein are incorporated herein by reference to the extent allowed by law fOr the purpose of describing and disclosing the compositions, compounds, methods, and similar information reported therein that might be used with the present invention, However, nothing herein is to be construed as an admission that the invention is not entitled to antedate such _disclosure by virtue of prior invention, EXAMPI,ES
[007 This invention can be Anther illustrated by the following examples of preferred embodiments thereof, although it will be understood that these examples are included merely fOr purposes of illustration and are not intended to limit the scope of the invention Unless otherwise specifically indicated, Example 1.
WON The study involved three groups of cats; Group I) cats on -a dry control Mod.
Group 2) cats on. a dry food fortified with approximately 65 ppm of lipoic acid, and Group 3) cats on a dry fOod fortified with approximately 650 ppm of lipoic acid on a dry Matter basis, All cats were fed control food for a two week baseline period at the end of which time iMITItine function assays were performed. One group of cats was then switched to the 65 ppm test food, one group to the 650 ppm test food and one group remained, on control and all were fed for another 6 weeks at which time the baseline teats were performed again, fOO-791 The administration of lipoic acid to old cats improved lymphocyte proliferation activity, which. may improve immune fanction. Most notably the effect of lipoi.c acid on improved lymphocyte proliferation in healthy cats at a .single level of inclusion (le, g 65 ppm).
100801 As illustrated in Figu.re 1, the inclusion of lipoic acid into feline pet foods at 65 ppm and 650 ppm for 6 weeks had no adverse effects on body-Nei& for cats.
lO08.11 Figure 2 illustrates the effect of inclusion of 65 ppm and 650 ppm in diets and time on Coneanavalin A. stimulation.. There was.. significant difference between the groups at the beginning of the study or at the end. However, the cats on the 65 ppm lipoic acid inclusion had a significant increase in Concanavalin A-activated lymphocyte proliferation compared to baseline. Cats on the 650 ppm also displayed an increase.
Accordingly, based on the Con.canavalin A-activated lymphocyte proliferation, the 11;
addition of 65 ppm or 650 ppm lipoic acid to a cat food composition could increase the immune response of cats.
100821 Figure 3 illustrates that pit,tohaemaplutinin (PHA) stimulation showed no significant difference between groups m beginning or end. The illustrative group administered 65 ppm lipoic acid had a significant increase in iyint-thocyte proliferation between baseline and 6 weeks of ifItVreetiti011. Accord-LI:1.0y, based on the PHA-activated lymphocyte proliferation, the addition of $5 ppm or 650 ppm. lipoic acid to a cat fbod composition could increase the immune response of cats [00831 Figure 4 illustrates Pokeweed Kitogen stimulation was different between groups (ANOVA P-(0.05) at the beginning. but not the end of the. study. The group with the lowest starting mean was the 65 ppm group. Subsequently,. lymphocyte proliferation in the group administered 65 ppm lipoic acid was significantly increased compared to baseline after 6 weeks time. Accordingly, based on the Pokeweed mitogen-activated lymphocyte proliferation, the addition of 65 ppm or 650 ppm lipoic acid to a cat fOod.
composition could increase the immune response of cats [00841 :Figure 5a and 5b illustrate natural killer cell activity. Based on the illustrative studies, no significant changes were detected from baseline to end of study for the 10:1 stimulation rate; however, all p values were less than 0.1: All changes betweenbaseline and end of study were significant for all groups at the 50:1 stimulation rate.
[00851 Figure 6 illustrates graphs for representative Comet assays. Iwo illustrative assays were performed: (1) inherent DNA damage and (2) .hydrogen peroxide challenged damage. Analysis of the data showed that all head DNA for all diets increased significantly (P<0.05) over the duration of the. study for both. In addition, all tail DNA tail length. and Olive tail momenta decreased during the duration of the study for both control and hydrogen peroxide challenged comet tests. However,. there were no significant differences between groups at either the beginning or end for any of the comet measures.
In addition, ANOVA analysis of the change over time (difilrence pre-post) showed no significant difkrence via t-test for each comet variable under control and hydrogen peroxide challenge conditions.
[00861 in the specification, there have been disclosed typical preferred embodiments of the invention and, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes-of limitation, the scope of the invention being set forth in the following. claims. Obviously many modifications and variations of the present invention are possible in light of the above teachings, it is therefore to be understood that within the scope of the appended claims the invention may be practiced otherwise than as specifically described,
Claims (14)
1. A composition for use in improving immune function in a feline in need thereof, wherein the improvement in immune function comprises increasing lymphocyte proliferation, which composition comprises an effective amount of lipoic acid or a salt thereof, wherein said effective amount is effective in improving immune function in a feline.
2. The composition for use of claim 1, wherein the effective amount is from 25 ppm to 2600 ppm of lipoic acid or a salt thereof.
3. The composition for use of claim 1 or 2, wherein the effective amount is from 50 ppm to 1200 ppm of lipoic acid or a salt thereof.
4. The composition for use of any one of claims 1 to 3, wherein the effective amount is from 65 ppm to 650 ppm of lipoic acid or a salt thereof.
5. The composition for use of any one of claims 1 to 4, wherein the lipoic acid or salt thereof is part of the feline's daily diet.
6. The composition for use of claim 5, wherein the daily diet comprises lipoic acid or salt thereof in an amount of greater than 25 ppm on a dry weight basis.
7. The composition for use of any one of claims 1 to 6, wherein the composition is a dry food composition.
8. The composition for use of any one of claims 1 to 7, wherein the feline is an older feline.
9. A composition comprising an effective amount of lipoic acid or a salt thereof to improve immune function in a feline, wherein said effective amount of lipoic acid is 65 ppm, and wherein the improvement in immune function comprises increasing lymphocyte proliferation.
10. A composition comprising an effective amount of lipoic acid or a salt thereof to improve immune function in a feline, wherein said effective amount of lipoic acid is 650 ppm, and wherein the improvement in immune function comprises increasing lymphocyte proliferation.
11. The composition of claim 9 or claim 10, wherein the composition is a food composition.
12. The composition of claim 11, wherein the food composition is a dry food composition.
13. The composition of claim 11, wherein the food composition is extruded.
14. The composition of claim 11, wherein the food composition is canned.
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| US12/353,351 US20090176864A1 (en) | 2004-11-24 | 2009-01-14 | Methods For Improving Hepatic and Immune Function In An Animal |
| US12/353,351 | 2009-01-14 | ||
| PCT/US2010/020993 WO2010083277A2 (en) | 2009-01-14 | 2010-01-14 | Methods for improving hepatic and immune function in an animal |
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2009
- 2009-01-14 US US12/353,351 patent/US20090176864A1/en not_active Abandoned
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2010
- 2010-01-14 RU RU2011134077/13A patent/RU2485797C2/en not_active IP Right Cessation
- 2010-01-14 CN CN2010800048871A patent/CN102281769A/en active Pending
- 2010-01-14 CA CA2843448A patent/CA2843448A1/en not_active Abandoned
- 2010-01-14 DK DK10700915.1T patent/DK2387325T3/en active
- 2010-01-14 WO PCT/US2010/020993 patent/WO2010083277A2/en not_active Ceased
- 2010-01-14 JP JP2011546323A patent/JP5791520B2/en active Active
- 2010-01-14 ES ES10700915.1T patent/ES2603986T3/en active Active
- 2010-01-14 BR BRPI1007294-2A patent/BRPI1007294A2/en not_active Application Discontinuation
- 2010-01-14 AU AU2010204766A patent/AU2010204766B2/en active Active
- 2010-01-14 CN CN201610320105.4A patent/CN106036037A/en active Pending
- 2010-01-14 EP EP10700915.1A patent/EP2387325B1/en active Active
- 2010-01-14 CA CA2749280A patent/CA2749280C/en active Active
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2011
- 2011-02-17 US US13/029,503 patent/US20110135785A1/en not_active Abandoned
- 2011-06-22 ZA ZA2011/04624A patent/ZA201104624B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP5791520B2 (en) | 2015-10-07 |
| WO2010083277A2 (en) | 2010-07-22 |
| AU2010204766A1 (en) | 2011-07-21 |
| WO2010083277A3 (en) | 2011-01-06 |
| ES2603986T3 (en) | 2017-03-02 |
| ZA201104624B (en) | 2015-02-25 |
| EP2387325A2 (en) | 2011-11-23 |
| BRPI1007294A2 (en) | 2015-08-25 |
| RU2011134077A (en) | 2013-02-20 |
| CN102281769A (en) | 2011-12-14 |
| CA2749280A1 (en) | 2010-07-22 |
| JP2012515211A (en) | 2012-07-05 |
| RU2485797C2 (en) | 2013-06-27 |
| CN106036037A (en) | 2016-10-26 |
| US20090176864A1 (en) | 2009-07-09 |
| EP2387325B1 (en) | 2016-08-17 |
| US20110135785A1 (en) | 2011-06-09 |
| AU2010204766B2 (en) | 2013-01-31 |
| CA2843448A1 (en) | 2010-07-22 |
| DK2387325T3 (en) | 2016-12-05 |
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